Anesthesia Pharmacology: Renal Pharmacology
Thiazides inhibit NaCl transport at the distal convoluted tubule
Prototypical thiazide: hydrochlorothiazide
Secreted by the organic acid secretory system
Competes with uric acid for secretion, uric acid secretory rates may decline.
Differences between thiazides:
Chlorothiazide (Diuril): less lipid soluble (requires relatively large doses)
Chlorthalidone (Hygroton): slowly absorbed -- longer duration of action
Indapamide (Lozol): mainly biliary secretion
Diuretic action: Inhibition of NaCl reabsorption from the distal convoluted tubule (luminal side).
Enhanced calcium reabsorption in the distal convoluted tubule (unknown mechanism).
Thiazides infrequently cause hypercalcemia but can unmask hypercalcemia due to other causes such as carcinoma, sarcoidosis, or hyperparathyroidism.
Congestive heart failure
Nephrolithiasis (due to idiopathic hypercalciuria
Nephrogenic diabetes insipidus
Hypokalemic metabolic alkalosis and hyperuricemia
Impaired carbohydrate tolerance
May induce hyperglycemia associated with:
Impaired pancreatic insulin release
Decreased tissue glucose utilization
Hyperglycemia may be partially reversed by correcting a hypokalemic state
5% to 15% increase in serum cholesterol and an increase in low-density lipoproteins.
Significant adverse effect, occasionally life-threatening
Hypovolemia-induced increase in ADH
Reduced renal diluting capacity
Prevention: decreasing the drug dose or limiting fluid intake
Thiazides are sulfonamides: cross-reactivity within the group
Extremely rare reactions:
Acute necrotizing pancreatitis
Jackson, E.K. Diuretics In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp. 685- 713
Jackson, E.K. Vasopressin and Other Agents Affecting the Renal Conservation of Water In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.715-732
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